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Chemokine receptors expression analysis reveals heterogeneity among central memory CD8 T cells, identifying different migratory patterns between HIV-infected patients

Christine Bourgeois

Statement of the Problem: Among HIV-infected patients, a rare proportion of patients (<0.5%) are able to spontaneously control the virus, in
the absence of antiretroviral treatment (ART). Numerous studies aim to decipher the crucial difference in the immune responses developing in
these HIV-controllers (HIC) patients. Memory differentiation, cytotoxic function, exhaustion and senescence profile of the T cell compartment
in the various groups of patients have been evaluated. Recent publications demonstrate the importance of the migratory phenotype to identify
crucial CD8 T cell responses in the context of chronic infection. The objective of the study was to readdress the functional activity of CD8 T cell in
HIV infection by evaluating the chemokine receptor expression. The aim was to determine whether HIC patients might differ from ART-treated
patients when considering CD8 T cell migratory properties. Methodology & Theoretical Orientation: 37 HIV-infected patients including HIC or
ART patients and 15 healthy subjects were studied. The expression of CXCR3, CXCR5 and CX3CR1 was evaluated in combination with standard
markers of T cell memory differentiation (CCR7 (and CD62L), CD45RO, CD27, CD28) and exhaustion (PD-1, TIGIT). Flow cytometry was performed
on fresh whole blood samples. Findings: When performing tSNE analyses, we observed that the central memory (Tcm) CD8 T cell compartment
included highly heterogeneous clusters. The analyses of diverse chemokine receptors confirmed this heterogeneity in particular among CXCR3,
CXCR5 or CXCR3/CXCR5 coexpressing cells. HIV infected patients, both HIC and ART, exhibited a higher fraction of CXCR3+/CXCR5+ cells among
Tcm than HD. Interestingly, HIC patients exhibited lower proportion of CXCR3+/CXCR5- among Tcm than ART patients. Conclusion & Significance:
The difference in the expression of chemokine receptors on Tcm CD8 T cells in HIC versus ART patients may reflect different homing properties
and may directly impact the quality of CD8 T cell responses.