TY - JOUR
T1 - Cardiac morbidity in HIV infection is associated with checkpoint inhibitor LAG-3 on CD4 T cells
AU - Pallikkuth, Suresh
AU - Pahwa, Rajendra
AU - Kausalya, Bagavathi
AU - Saravanan, Shanmugam
AU - Pan, Li
AU - Vignesh, R.
AU - Iqbal, Syed
AU - Solomon, Sunil S.
AU - Murugavel, Kailapuri G.
AU - Poongulali, Selvamuthu
AU - Kumarasamy, Nagalingeswaran
AU - Pahwa, Savita
N1 - Publisher Copyright:
© 2018 Pallikkuth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/10
Y1 - 2018/10
N2 - Recent findings point to a role of Checkpoint Inhibitor (CPI) receptors at the tissue level in immune homeostasis. Here we investigated the role of CPI molecules on immune cells in relation to cardiac function. Participants recruited in Chennai, India consisted of HIV+ ART naive viremic (Gp1 n = 102), HIV+ on ART, virologically suppressed (Gp2, n = 172) and HIV negative healthy controls (Gp3, n = 64). A cross-sectional analysis of cardiac function, arterial resistance and immunologic assessment of CPI expressing T cells was performed. Data indicate that ART naive exhibited cardiac function impairment and greater arterial stiffness than the other groups. Frequencies of CD4+ T cells expressing LAG-3 and PD1 were higher in ART naïve while TIGIT and TIM3 were similar among the patient groups. LAG-3+, PD1+ and dual LAG-3+PD1+ CD4 T cells were inversely correlated with cardiac function and arterial elasticity and directly with arterial stiffness in ART naïve participants and with arterial elasticity in virally suppressed group on ART. We conclude that HIV induced upregulation of LAG-3 singly or in combination with PD1 in immune cells may regulate cardiac health and warrant mechanistic investigations. The implications of these findings have bearing for the potential utility of anti-LAG-3 immunotherapy for cardiac dysfunction in chronic HIV infection.
AB - Recent findings point to a role of Checkpoint Inhibitor (CPI) receptors at the tissue level in immune homeostasis. Here we investigated the role of CPI molecules on immune cells in relation to cardiac function. Participants recruited in Chennai, India consisted of HIV+ ART naive viremic (Gp1 n = 102), HIV+ on ART, virologically suppressed (Gp2, n = 172) and HIV negative healthy controls (Gp3, n = 64). A cross-sectional analysis of cardiac function, arterial resistance and immunologic assessment of CPI expressing T cells was performed. Data indicate that ART naive exhibited cardiac function impairment and greater arterial stiffness than the other groups. Frequencies of CD4+ T cells expressing LAG-3 and PD1 were higher in ART naïve while TIGIT and TIM3 were similar among the patient groups. LAG-3+, PD1+ and dual LAG-3+PD1+ CD4 T cells were inversely correlated with cardiac function and arterial elasticity and directly with arterial stiffness in ART naïve participants and with arterial elasticity in virally suppressed group on ART. We conclude that HIV induced upregulation of LAG-3 singly or in combination with PD1 in immune cells may regulate cardiac health and warrant mechanistic investigations. The implications of these findings have bearing for the potential utility of anti-LAG-3 immunotherapy for cardiac dysfunction in chronic HIV infection.
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U2 - 10.1371/journal.pone.0206256
DO - 10.1371/journal.pone.0206256
M3 - Article
C2 - 30379878
AN - SCOPUS:85055797355
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 10
M1 - e0206256
ER -