Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection.
HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common opportunistic pathogens, cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB). CMV-specific CD4 T cells persisted after HIV infection, whereas MTB-specific CD4 T cells were depleted rapidly. CMV-specific CD4 T cells expressed a mature phenotype and produced very little IL-2, but large amounts of MIP-1β. In contrast, MTB-specific CD4 T cells were less mature, and most produced IL-2 but not MIP-1β. Staphylococcal enterotoxin B-stimulated IL-2-producing cells were more susceptible to HIV infection in vitro than MIP-1β-producing cells. Moreover, IL-2 production was associated with expression of CD25, and neutralization of IL-2 completely abrogated productive HIV infection in vitro. HIV DNA was found to be most abundant in IL-2-producing cells, and least abundant in MIP-1β-producing MTB-specific CD4 T cells from HIV-infected subjects with active tuberculosis. These data support the hypothesis that differences in function affect the susceptibility of pathogen-specific CD4 T cells to HIV infection and depletion in vivo, providing a potential mechanism to explain the rapid loss of MTB-specific CD4 T cells after HIV infection.
Immunology Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. geldmacher@lrz.uni-muenchen.de
Christof
C
Geldmacher
Njabulo
N
Ngwenyama
Alexandra
A
Schuetz
Constantinos
C
Petrovas
Klaus
K
Reither
Edwin J
EJ
Heeregrave
Joseph P
JP
Casazza
David R
DR
Ambrozak
Mark
M
Louder
William
W
Ampofo
Georgios
G
Pollakis
Brenna
B
Hill
Erica
E
Sanga
Elmar
E
Saathoff
Leonard
L
Maboko
Mario
M
Roederer
William A
WA
Paxton
Michael
M
Hoelscher
Richard A
RA
Koup
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology; D005434:Flow Cytometry; D018628:Gene Dosage; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D009894:Opportunistic Infections / Q000150:complications / Q000276:immunology; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D054407:Chemokine CCL4; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens