CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection.
Decreased CD4(+) T cell counts are the best marker of disease progression during HIV infection. However, CD4(+) T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4(+) T cell subsets influences disease severity. CD4(+) T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127(+)CD25(low/-) subset includes IL-2-producing naive and central memory T cells; the CD127(-)CD25(-) subset includes mainly effector T cells expressing perforin and IFN-gamma; and the CD127(low)CD25(high) subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4(+)CD127(-)CD25(-) T cells that is related to an absolute decline of CD4(+)CD127(+)CD25(low/-) T cells. Interestingly, this expansion of CD4(+)CD127(-) T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4(+)CD127(-)CD25(-) T cells correlated directly with the levels of total CD4(+) T cell depletion and immune activation. CD4(+)CD127(-)CD25(-) T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4(+) T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4(+) T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4(+) T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals.
Dunham
Richard M
RM
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cervasi
Barbara
B
Brenchley
Jason M
JM
Albrecht
Helmut
H
Weintrob
Amy
A
Sumpter
Beth
B
Engram
Jessica
J
Gordon
Shari
S
Klatt
Nichole R
NR
Frank
Ian
I
Sodora
Donald L
DL
Douek
Daniel C
DC
Paiardini
Mirko
M
Silvestri
Guido
G
D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016665:Cercocebus atys; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit