HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapies

Changes in CD4+ T-cell surface marker phenotype and antigen receptor (TCR) repertoire were examined during the course of HIV infection and following therapy. A preferential decline in naive CD4+ T cells was noted as disease progressed. Following protease inhibitor therapy, naive CD4+ T cells increased only if they were present before initiation of therapy. Disruptions of the CD4+ TCR repertoire were most prevalent in patients with the lowest CD4+ T-cell counts. Antiviral or IL-12 therapy-induced increases in CD4+ T-cell counts led to only minor changes in previously disrupted repertoires. Thus, CD4+ T-cell death mediated by HIV-1 infection may result in a preferential decline in the number of naive CD4+ T cells and disruptions of the CD4+T-cell repertoire that are not immediately corrected by antiviral or immune-based therapies.

[1]  S. Steinberg,et al.  Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. , 1995, The New England journal of medicine.

[2]  G. Kitas,et al.  Production of lymphokine mRNA by CD45R+ and CD45R- helper T cells from human peripheral blood and by human CD4+ T cell clones. , 1989, Journal of immunology.

[3]  T. Waldmann,et al.  Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. , 1985, The New England journal of medicine.

[4]  J. Sprent,et al.  Lymphocyte life-span and memory. , 1994, Science.

[5]  A. Fauci,et al.  Analysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific V beta segments in CD4+ T cells of the virus-positive twins. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Condra,et al.  In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors , 1995, Nature.

[7]  R. Zinkernagel.  The role of antigen in maintaining T cell memory. , 1994, Developments in biological standardization.

[8]  Beverley Pc.  Functional analysis of human T cell subsets defined by CD45 isoform expression. , 1992, Seminars in immunology.

[9]  S. Roman-Roman,et al.  An experimentally validated panel of subfamily‐specific oligonucleotide primers (Vα1‐w29/Vβ1‐w24) for the study of human T cell receptor variable V gene segment usage by polymerase chain reaction , 1992, European journal of immunology.

[10]  A. Régnault,et al.  Molecular detection and in vivo analysis of the specific T cell response to a protein antigen , 1992, European journal of immunology.

[11]  J. Sprent,et al.  Turnover of Naive-and Memory-phenotype T Cells , 1994 .

[12]  M. Puoti,et al.  Selective depletion in HIV infection of T cells that bear specific T cell receptor V beta sequences. , 1991, Science.

[13]  M. Roederer,et al.  CD8 naive T cell counts decrease progressively in HIV-infected adults. , 1995, The Journal of clinical investigation.

[14]  A. Fauci,et al.  The T cell receptor Vβ repertoire in HIV-1 infection and disease , 1993 .

[15]  D. Longo,et al.  Kinetics of recovery of CD4+ T cells in peripheral blood of deoxycoformycin-treated patients. , 1991, Journal of the National Cancer Institute.

[16]  J. Metcalf,et al.  Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. , 1996, The New England journal of medicine.

[17]  J. Sprent.  Lifespans of naive, memory and effector lymphocytes. , 1993, Current opinion in immunology.

[18]  J. Justement,et al.  Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Laurence,et al.  Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V β expression , 1992, Nature.

[20]  A. Dalgleish,et al.  The role of host immune responses in determining the outcome of HIV infection. , 1996, Immunology today.

[21]  R. Detels,et al.  Phenotypically defined memory CD4+ cells are not selectively decreased in chronic HIV disease. , 1994, Journal of Acquired Immune Deficiency Syndromes.

[22]  J. Cabaniols,et al.  Public and private V beta T cell receptor repertoires against hen egg white lysozyme (HEL) in nontransgenic versus HEL transgenic mice , 1994, The Journal of experimental medicine.

[23]  C. Fox,et al.  Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse , 1993, The Journal of experimental medicine.

[24]  M. Pope,et al.  Enhanced HIV-1 replication in Vβ12 T cells due to human cytomegalovirus in monocytes: Evidence for a putative herpesvirus superantigen , 1995, Cell.

[25]  I. Trowbridge,et al.  CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. , 1994, Annual review of immunology.

[26]  M. Clerici,et al.  Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging. , 1989, The Journal of clinical investigation.

[27]  A. McLean,et al.  In vivo estimates of division and death rates of human T lymphocytes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[28]  K. Mehta,et al.  Human immunodeficiency virus 1 reservoir in CD4+ T cells is restricted to certain V beta subsets. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Jaap,et al.  Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs. , 1988, The Journal of clinical investigation.

[30]  T. Springer,et al.  Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. , 1988, Journal of immunology.

[31]  P. Kourilsky,et al.  Oligoclonality of tumor-infiltrating lymphocytes from human melanomas. , 1994, Journal of immunology.

[32]  M. Clerici,et al.  Human immunodeficiency virus infection in the US Air Force: seroconversions, clinical staging, and assessment of a T helper cell functional assay to predict change in CD4+ T cell counts. , 1991, The Journal of infectious diseases.

[33]  R. Rabin,et al.  Altered representation of naive and memory CD8 T cell subsets in HIV-infected children. , 1995, The Journal of clinical investigation.

[34]  M. Helbert.  T-cell receptor variable gene products and early HIV-1 infection. , 1992 .

[35]  M. Zöller,et al.  The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P. Marrack,et al.  Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. , 1989, Proceedings of the National Academy of Sciences of the United States of America.